Twist1-Haploinsufficiency Selectively Enhances the Osteoskeletal Capacity of Mesoderm-derived Parietal Bone through Downregulation of Fgf23

Purpose: This study investigates the postnatal impact of Twist1 haploinsufficiency on the osteoskeletal ability and regeneration on two calvarial bones arising from tissues of different embryonic origin: the neural crest-derived frontal and the mesoderm-derived parietal bones. Results: Twist1 haplonsufficiency selectively enhanced osteogenic and tissue regeneration ability of mesoderm-derived parietal bones. Twist1 haplonsufficiency triggers its selective activity on mesoderm-derived parietal bone through downregulation of the bone-derived hormone Fgf23. Conclusions: Twist1 haploinsufficiency preferentially triggers osteogenic induction of parietal bones which may be beneficial to optimize treatments for skeletal regeneration, reconstruction and repair of mesoderm-derived bone, as well as to alleviate skeletal abnormalities caused by Twist1 haploinsufficiency. Total RNA profiles of 21-day old wild type (WT) and Twist1+/- mice were generated by sequencing using Illumina NextSeq.

研究目的：本研究探讨Twist1单倍体不足（Twist1 haploinsufficiency）对两块源自不同胚胎起源组织的颅盖骨——神经嵴来源额骨与中胚层来源顶骨——的骨骼功能及再生能力的出生后影响。
研究结果：Twist1单倍体不足可选择性增强中胚层来源顶骨的成骨与组织再生能力。其通过下调骨源性激素成纤维细胞生长因子23（Fgf23），对中胚层来源的顶骨发挥选择性调控作用。
研究结论：Twist1单倍体不足可优先诱导顶骨的成骨分化，该发现或有助于优化中胚层来源骨的骨骼再生、重建与修复治疗方案，同时可缓解由Twist1单倍体不足引发的骨骼异常。
本研究采用Illumina NextSeq测序技术，获取了21日龄野生型（wild type, WT）小鼠与Twist1+/-小鼠的总RNA转录组图谱。